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Related Experiment Video

Updated: Jul 3, 2025

Exogenous Administration of Microsomes-associated Alpha-synuclein Aggregates to Primary Neurons As a Powerful Cell Model of Fibrils Formation
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Stochastic Optical Reconstruction Microscopy Imaging of Multiple System Atrophy Inclusions Suggests Stepwise

Benoît Vovard1,2, Alexia Bodin1,2, Julien Gouju2,3

  • 1Univ Angers, Equipe MitoLab, Unité MitoVasc, Inserm U1083, CNRS 6015, SFR ICAT, Angers, France.

Movement Disorders : Official Journal of the Movement Disorder Society
|February 15, 2024
PubMed
Summary

This study used STORM microscopy to investigate α-synuclein inclusions in multiple system atrophy (MSA). Findings reveal a stepwise aggregation process in both glial (GCI) and neuronal (NCI) cells, suggesting a common mechanism.

Keywords:
Parkinson's diseaseSTORMdementia with Lewy bodiesmultiple system atrophyα‐synuclein

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Area of Science:

  • Neuroscience
  • Cell Biology
  • Pathology

Background:

  • Multiple system atrophy (MSA) is characterized by glial (GCI) and neuronal (NCI) α-synuclein inclusions.
  • The precise architecture and composition of these inclusions are not well understood.
  • Understanding these inclusions is crucial for deciphering MSA pathogenesis.

Purpose of the Study:

  • To characterize the nanoscale organization of α-synuclein inclusions in MSA.
  • To investigate the potential common aggregation mechanisms in glial and neuronal cells.

Main Methods:

  • Stochastic optical reconstruction microscopy (STORM) was employed.
  • Cryopreserved brain sections from MSA patients were analyzed.
  • Nanoscale organization of GCI and NCI was examined.

Main Results:

  • STORM imaging revealed a dense, cross-linked internal structure of α-synuclein in all GCI and NCI.
  • The architecture of hyperphosphorylated α-synuclein (p-αSyn) inclusions was similar in glial and neuronal cells.
  • A common stepwise intracellular aggregation sequence, starting from the perinuclear area, was observed in both cell types.
  • Higher mitochondrial density was noted in GCI and NCI compared to unaffected cells, suggesting organelle recruitment.

Conclusions:

  • These findings provide the first STORM images of GCI and NCI in MSA.
  • The results suggest a stepwise α-synuclein aggregation process common to both glial and neuronal cells in MSA.
  • This sheds light on the aggregation mechanisms underlying MSA pathology.